Chapter 109. Disorders of Platelets and Vessel Wall (Part 8) Hemolytic Uremic Syndrome HUS is a syndrome characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. It is seen predominantly in children and in most cases is preceded by an episode of diarrhea, often hemorrhagic in nature. Escherichia coli O157:H7 is the most frequent, although not only, etiologic serotype. HUS not associated with diarrhea (termed DHUS) is more heterogeneous in presentation and course. Some children who develop DHUS have been found to have mutations in genes encoding Factor H, a soluble complement regulator, and membrane cofactor protein that is mainly expressed in the kidney. Hemolytic Uremic Syndrome: Treatment Treatment of HUS is primarily supportive. In D+HUS, many (~40%) children require at least some period of support with dialysis; however, the overall mortality is <5%. In D–HUS the mortality is higher, approximately 26%. Plasma infusion or plasma exchange has not been shown to alter the overall course. ADAMTS13 levels are generally reported to be normal in HUS, although occasionally they have been reported to be decreased. As ADAMTS13 assays improve, they may help in defining a subset that better fits a TTP diagnosis and may respond to plasma exchange. Thrombocytosis Thrombocytosis is almost always due to (1) iron deficiency; (2) inflammation, cancer, or infection (reactive thrombocytosis); or (3) an underlying myeloproliferative process [essential thrombocythemia or polycythemia vera (Chap. 103)] or, rarely, the 5q-myelodysplastic process (Chap. 102). Patients presenting with an elevated platelet count should be evaluated for underlying inflammation or malignancy, and iron deficiency should be ruled out. Thrombocytosis in response to acute or chronic inflammation has not been associated with an increased thrombotic risk. In fact, patients with markedly elevated platelet counts (>1.5 million), usually seen in the setting of a myeloproliferative disorder, have an increased risk of bleeding. This appears to be due, at least in part, to acquired von Willebrand disease (vWD) due to platelet- vWF adhesion and removal. Qualitative Disorders of Platelet Function Inherited Disorders of Platelet Function Inherited platelet function disorders are thought to be relatively rare, although the prevalence of mild disorders of platelet function is unclear, in part because our testing for such disorders is suboptimal. Rare qualitative disorders include the autosomal recessive disorders Glanzmann's thrombasthenia (absence of the platelet GpIIbIIIa receptor) and Bernard Soulier syndrome (absence of the platelet GpIb-IX-V receptor). Both are inherited in an autosomal recessive fashion and present with bleeding symptoms in childhood. Platelet storage pool disorder (SPD) is the classic autosomal dominant qualitative platelet disorder. This results from abnormalities of platelet granule formation. It is also seen as a part of inherited disorders of granule formation, such as Hermansky-Pudlak syndrome. Bleeding symptoms in SPD are variable but often mild. The most common inherited disorders of platelet function are disorders that prevent normal secretion of granule content. Few of the abnormalities have been dissected at the molecular level, but these are likely due to multiple abnormalities. They are usually described as secretion defects. Bleeding symptoms are usually mild in nature. Inherited Disorders of Platelet Dysfunction: Treatment Bleeding symptoms or prevention of bleeding in patients with severe dysfunction frequently requires platelet transfusion. Care is taken to limit the risk of alloimmunization by limiting exposure and using prestorage leukodepleted platelets for transfusion. Platelet disorders associated with milder bleeding symptoms frequently respond to desmopressin [1-deamino-8-D- arginine vasopressin (DDAVP)]. DDAVP increases plasma vWF and FVIII levels; whether it also has a direct effect on platelet function is unknown. Particularly for mucosal bleeding symptoms, antifibrinolytic therapy (epsilon-aminocaproic acid or tranexamic acid) is used alone or in conjunction with DDAVP or platelet therapy. Acquired Disorders of Platelet Function Acquired platelet dysfunction is common, usually due to medications, either intentionally, as with antiplatelet therapy, or unintentionally, as with high dose penicillins. Acquired platelet dysfunction occurs in uremia. This is likely multifactorial, but the resultant effect is defective adhesion and activation. The platelet defect is improved most by dialysis, but may also be improved by increasing the hematocrit to 27–32%, giving DDAVP (0.3 µg/kg), or use of conjugated estrogens. Platelet dysfunction also occurs with cardiopulmonary bypass due to the effect of the artificial circuit on platelets, and bleeding symptoms respond to platelet transfusion. Platelet dysfunction seen with underlying hematologic disorders can result from nonspecific interference by circulating paraproteins or intrinsic platelet defects in myeloproliferative and myelodysplastic syndromes. . Chapter 109. Disorders of Platelets and Vessel Wall (Part 8) Hemolytic Uremic Syndrome HUS is a syndrome characterized by acute renal failure, microangiopathic hemolytic anemia, and. Disorders of Platelet Function Inherited Disorders of Platelet Function Inherited platelet function disorders are thought to be relatively rare, although the prevalence of mild disorders of. for such disorders is suboptimal. Rare qualitative disorders include the autosomal recessive disorders Glanzmann's thrombasthenia (absence of the platelet GpIIbIIIa receptor) and Bernard